Fig. 4

Immunohistochemistry staining of DNA damage response proteins. a H&E and Ki67 staining from a CR patient (left panels) and a TF patient (right panels) demonstrate characteristic bone marrow morphology and cell proliferation profile. In both CR and TF patient samples collected at baseline, tumor cells actively proliferate as shown by intensive Ki67 staining. In CR patient, complete remission of tumor cells was achieved at day 12 with few dividing cells visible; at recovery stage, high level of Ki67 staining in clustered cells is typical of active hematopoiesis. In TF patient, although complete remission was not achieved, tumor cell density and cell proliferation (Ki67) were significantly reduced in day 12 bone marrow. b Increased nuclear staining of major TSPs p53, SMAD4, Rb, and p21 were demonstrated in bone marrow biopsy samples collected from a TF patient at baseline and at day 12. Less cells stained positive for topoisomerase IIα after induction at day 12, suggesting reduced cell proliferation. Increased phosphorylated γH2A.X (Ser 139) staining after induction indicate more DNA damage at day 12